EA035899B1 - Производные диаминопиридина в качестве ингибиторов jak - Google Patents

Производные диаминопиридина в качестве ингибиторов jak Download PDF

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Publication number: EA035899B1
Authority: EA; Eurasian Patent Office
Prior art keywords: pharmaceutically acceptable; disease; acceptable salt; compound according; present
Prior art date: 2015-11-26

Application number

EA201891258A

Other languages

English (en)

Russian (ru)

Other versions

EA201891258A1 (ru

Inventor

Гебхард Тома

Original Assignee

Новартис Аг

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2015-11-26

Filing date

2016-11-24

Publication date

2020-08-28

2016-11-24 Application filed by Новартис Аг filed Critical Новартис Аг

2018-10-31 Publication of EA201891258A1 publication Critical patent/EA201891258A1/ru

2020-08-28 Publication of EA035899B1 publication Critical patent/EA035899B1/ru

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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A—HUMAN NECESSITIES
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- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Pulmonology (AREA)
Immunology (AREA)
Diabetes (AREA)
Dermatology (AREA)
Physical Education & Sports Medicine (AREA)
Rheumatology (AREA)
Epidemiology (AREA)
Orthopedic Medicine & Surgery (AREA)
Hematology (AREA)
Endocrinology (AREA)
Pain & Pain Management (AREA)
Neurology (AREA)
Urology & Nephrology (AREA)
Otolaryngology (AREA)
Obesity (AREA)
Emergency Medicine (AREA)
Transplantation (AREA)
Vascular Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyridine Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

EA201891258A 2015-11-26 2016-11-24 Производные диаминопиридина в качестве ингибиторов jak EA035899B1 (ru)

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EP15196542		2015-11-26
PCT/IB2016/057105 WO2017089985A1 (en)	2015-11-26	2016-11-24	Diamino pyridine derivatives

Publications (2)

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EA201891258A1 EA201891258A1 (ru)	2018-10-31
EA035899B1 true EA035899B1 (ru)	2020-08-28

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US (3)	US10570096B2 (es)
EP (2)	EP3757097B1 (es)
JP (1)	JP6634157B2 (es)
KR (1)	KR102097878B1 (es)
CN (2)	CN112851578A (es)
AU (1)	AU2016359438B2 (es)
BR (1)	BR112018009540A2 (es)
CA (1)	CA3005159A1 (es)
CL (1)	CL2018001370A1 (es)
CO (1)	CO2018005354A2 (es)
CR (1)	CR20180285A (es)
CU (1)	CU24506B1 (es)
CY (1)	CY1123543T1 (es)
DK (1)	DK3380465T3 (es)
DO (1)	DOP2018000127A (es)
EA (1)	EA035899B1 (es)
EC (1)	ECSP18041731A (es)
ES (2)	ES2916582T3 (es)
HR (1)	HRP20201662T1 (es)
HU (1)	HUE052345T2 (es)
IL (1)	IL259360B (es)
LT (1)	LT3380465T (es)
MX (1)	MX379776B (es)
MY (1)	MY195905A (es)
PE (1)	PE20181071A1 (es)
PH (1)	PH12018501019B1 (es)
PL (2)	PL3757097T3 (es)
PT (2)	PT3757097T (es)
RS (1)	RS60946B1 (es)
RU (2)	RU2020124922A (es)
SA (1)	SA518391657B1 (es)
SG (1)	SG11201803760VA (es)
SI (1)	SI3380465T1 (es)
WO (1)	WO2017089985A1 (es)

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Publication number	Priority date	Publication date	Assignee	Title
AU2016359438B2 (en) *	2015-11-26	2019-05-02	Novartis Ag	Diamino pyridine derivatives
ES2998786T3 (en)	2019-01-11	2025-02-21	Novartis Ag	Lta4h inhibitor for the treatment or prevention of hidradenitis suppurativa
TW202342048A (zh)	2022-02-28	2023-11-01	瑞士商諾華公司	使用ｌｏｕ０６４治療化膿性汗腺炎之方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2014074660A1 (en) *	2012-11-08	2014-05-15	Bristol-Myers Squibb Company	ALKYL-AMIDE-SUBSTITUTED PYRIDYL COMPOUNDS USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFNα RESPONSES
WO2014074675A1 (en) *	2012-11-08	2014-05-15	Bristol-Myers Squibb Company	Heteroaryl substituted pyridyl compounds useful as kinase modulators

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2007524596A (ja)	2003-02-28	2007-08-30	トランスフォーム・ファーマシューティカルズ・インコーポレイテッド	共結晶医薬組成物
US7459562B2 (en)	2004-04-23	2008-12-02	Bristol-Myers Squibb Company	Monocyclic heterocycles as kinase inhibitors
KR101149295B1 (ko) *	2006-12-08	2012-07-05	아이알엠 엘엘씨	단백질 키나제 억제제로서의 화합물
ES2485040T3 (es)	2007-03-16	2014-08-12	The Scripps Research Institute	Inhibidores de cinasa de adhesión focal
WO2010058846A1 (ja) *	2008-11-21	2010-05-27	アステラス製薬株式会社	４，６-ジアミノニコチンアミド化合物
KR101361027B1 (ko)	2008-11-28	2014-02-11	코와 가부시키가이샤	피리딘-3-카르복시아미드 유도체
SG2014005318A (en)	2009-01-23	2014-03-28	Rigel Pharmaceuticals Inc	Compositions and methods for inhibition of the jak pathway
US8415381B2 (en) *	2009-07-30	2013-04-09	Novartis Ag	Heteroaryl compounds and their uses
US9102625B2 (en)	2010-11-01	2015-08-11	Portola Pharmaceuticals, Inc.	Nicotinamides as JAK kinase modulators
US9198911B2 (en)	2010-11-02	2015-12-01	The Trustees Of Columbia University In The City Of New York	Methods for treating hair loss disorders
JP2015534959A (ja)	2012-10-19	2015-12-07	エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト	Ｓｙｋの阻害剤
SG10201706897TA (en) *	2012-11-08	2017-09-28	Bristol Myers Squibb Co	Amide-substituted heterocyclic compounds useful as modulators of il-12, il-23 and/or ifn alph responses
US20140343034A1 (en)	2013-04-25	2014-11-20	Japan Tobacco Inc.	Skin barrier function improving agent
WO2014181287A1 (en)	2013-05-09	2014-11-13	Piramal Enterprises Limited	Heterocyclyl compounds and uses thereof
WO2014203132A1 (en)	2013-06-19	2014-12-24	Olema Pharmaceuticals, Inc.	Substituted benzopyran compounds, compositions and uses thereof
JP2015014960A (ja)	2013-07-05	2015-01-22	ソニー株式会社	情報処理装置、および記憶媒体
AU2014339897A1 (en)	2013-10-24	2016-04-21	Abbvie Inc.	JAK1 selective inhibitor and uses thereof
WO2016090173A1 (en)	2014-12-03	2016-06-09	Rxi Pharmaceuticals Corporation	Methods for the treatment of alopecia areata utilizing gene modulation approaches
AU2016359438B2 (en) *	2015-11-26	2019-05-02	Novartis Ag	Diamino pyridine derivatives

2016
- 2016-11-24 AU AU2016359438A patent/AU2016359438B2/en not_active Ceased
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- 2016-11-24 WO PCT/IB2016/057105 patent/WO2017089985A1/en not_active Ceased
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- 2016-11-24 SG SG11201803760VA patent/SG11201803760VA/en unknown
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- 2016-11-24 PT PT201855079T patent/PT3757097T/pt unknown
- 2016-11-24 RS RS20201234A patent/RS60946B1/sr unknown
- 2016-11-24 RU RU2018122953A patent/RU2730007C2/ru active
- 2016-11-24 HU HUE16805218A patent/HUE052345T2/hu unknown
- 2016-11-24 PL PL16805218T patent/PL3380465T3/pl unknown
- 2016-11-24 MY MYPI2018701770A patent/MY195905A/en unknown
- 2016-11-24 HR HRP20201662TT patent/HRP20201662T1/hr unknown
- 2016-11-24 PT PT168052181T patent/PT3380465T/pt unknown
- 2016-11-24 US US15/778,783 patent/US10570096B2/en active Active
- 2016-11-24 JP JP2018527091A patent/JP6634157B2/ja not_active Expired - Fee Related
- 2016-11-24 ES ES16805218T patent/ES2829052T3/es active Active
2018
- 2018-05-14 IL IL259360A patent/IL259360B/en active IP Right Grant
- 2018-05-21 DO DO2018000127A patent/DOP2018000127A/es unknown
- 2018-05-22 CO CONC2018/0005354A patent/CO2018005354A2/es unknown
- 2018-05-22 CL CL2018001370A patent/CL2018001370A1/es unknown
- 2018-05-23 SA SA518391657A patent/SA518391657B1/ar unknown
- 2018-05-31 EC ECIEPI201841731A patent/ECSP18041731A/es unknown
2020
- 2020-01-08 US US16/737,366 patent/US11274080B2/en active Active
- 2020-11-03 CY CY20201101039T patent/CY1123543T1/el unknown
2022
- 2022-02-22 US US17/677,538 patent/US20220177432A1/en not_active Abandoned

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2014074660A1 (en) *	2012-11-08	2014-05-15	Bristol-Myers Squibb Company	ALKYL-AMIDE-SUBSTITUTED PYRIDYL COMPOUNDS USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFNα RESPONSES
WO2014074675A1 (en) *	2012-11-08	2014-05-15	Bristol-Myers Squibb Company	Heteroaryl substituted pyridyl compounds useful as kinase modulators

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BENJAMIN J. DUGAN, DIANE E. GINGRICH, EUGEN F. MESAROS, KAREN L. MILKIEWICZ, MATTHEW A. CURRY, ALLISON L. ZULLI, PAWEL DOBRZANSKI,: "A Selective, Orally Bioavailable 1,2,4-Triazolo[1,5- a ]pyridine-Based Inhibitor of Janus Kinase 2 for Use in Anticancer Therapy: Discovery of CEP-33779", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, vol. 55, no. 11, 14 June 2012 (2012-06-14), pages 5243 - 5254, XP055131963, ISSN: 00222623, DOI: 10.1021/jm300248q *

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